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Park, Tae Joo
Developmental Morphogenesis Lab
Research Interests
  • Morphogenesis, chondrogenesis, ciliogenesis

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Blockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells

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Title
Blockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells
Author
Shin, HanhoHan, Ji HyeYoon, JuhwanSim, Hyo JungPark, Tae JooYang, SiyoungLee, Eun KyungKulkarni, Rohit N.Egan, Josephine M.Kim, Wook
Keywords
beta-cell function;  cannabinoid 1 receptor;  glucokinase;  glucose transporter 2;  insulin secretion
Issue Date
201804
Publisher
WILEY
Citation
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v.22, no.4, pp.2337 - 2345
Abstract
Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse beta-cell lines, human islets and CB1R-null (CB1R(-/-)) mice, we have now investigated the role of CB1Rs in modulating beta-cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP-1-mediated cAMP accumulation and insulin secretion as well as glucose-stimulated insulin secretion in mouse beta-cell lines and human islets. In addition, silencing CB1R in mouse cells resulted in an increased expression of pro-insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in cells lacking insulin receptor. Furthermore, CB1R(-/-) mice had increased pro-insulin, GCK and GLUT2 expression in cells. Our results suggest that CB1R signalling in pancreatic islets may be harnessed to improve beta-cell glucose responsiveness and preserve their function. Thus, our findings further support that blocking peripheral CB1Rs would be beneficial to beta-cell function in type 2 diabetes.
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DOI
http://dx.doi.org/10.1111/jcmm.13523
ISSN
1582-4934
Appears in Collections:
SLS_Journal Papers
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